Two- and three-dimensional polymer/hydrogel matrices provide a diverse scaffold that can be modified and refined for various purposes. Hydrogels can be applied to various medical, engineering, biological and chemical applications, such as drug or chemical delivery, tissue engineering, cell transplantation, wound healing and rheology modification (See, e.g.: Wu et al. (U.S. Pat. No. 6,030,634); Trollsas et al. (U.S. Pat. No. 6,458,889); Sehl et al. (U.S. Pat. No. 6,833,408); Stile & Healy (Biomacromolecules, 2001, 2(1): 185-194); Kim & Healy (Biomacromolecules, 2003, 4(5): 1214-1223); Li et al. (Biomaterials, 2005, 26: 3093-3104); Rosenblatt et al. (U.S. Pat. No. 5,807,581); Ulbrich et al. (U.S. Pat. No. 5,124,421); Lee & Vernon (Macromol. Biosci. 2005, 5(7):629-635); Cha et al. (U.S. Pat. No. 5,702,717); Jeong et al. (U.S. Pat. No. 6,841,617); each of which is herein incorporated by reference in its entirety).
Various kinds of thermoresponsive N-isopropylacrylamide (NIPA) copolymers are among an important class of bioengineering materials that have been the subject of many extensive investigations in the field of modern macromolecular bioengineering and biotechnology (See, e.g.: Monji N, Hoffman A S. Appl Biochem Biotechnol 1987; 14:107-20; Chen J-P, Hoffman A S. Biomaterials 1990; 11:631-4; Kim M R, Jeong J H, Park T G. Biotechnol Prog 2002; 18:495-500; Strauss U P, Schlesinger M S. J Phys Chem 1978; 82:1627-32; Katre N V. Adv Drug Delivery Rev 1993; 10:91-114; Delgado C, Francis G E, Fisher D. Crit Rev Therapeut Drug Carrier Syst 1992; 9:249-304; Kesim H, Rzaev Z M O, Dincer S, Piskin E. Polymer 2003; 44:2897-909; Dincer S., Koseli, V., Kesim H., Rzaev Z M O, Piskin E. Eur Polym J 2002; 38:43-52; Bulmus V. Patir S, Tuncel A, Piskin E. J Control Release 2001; 76:265-74; Lee B H, Vernon B. Macromol Biosci 2005; 5:629-635; Guan J, Hong Y, Ma Z, Wagner W R. Biomacromolecules 2008; 9:1283-1292.; Wang T, Wu D, Jiang X, Li X, Zhang J, Zheng Z, Zhuo R, Jiang H, Huang C. Eur J Heart Fail 2009; 11:14-19; Fujimoto K L, Ma Z, Nelson D M, Hashizume R, Guan J, Tobita K, Wagner W R. Biomaterials 2009; 30:4357-4368; Yang J, Webb J A, Ameer G A. Adv Mater 2004; 16:511-516; Yang J, Webb A, Pickerill S. Hageman G, Ameer G A. Biomaterials 2006; 27:1889-1898; herein incorporated by reference in their entireties).
PEG is commonly incorporated into medical implants to resist protein adsorption, platelet adhesion, and bacterial adhesion (Deible C R, Beckman E J, Russell A J, Wagner W R. J Biomed Mater Res 1998; 41:251-256; Han D K, Park I C D, Hubbell J A, Kim Y H. J Biomater Sci Polym Ed 1998; 9:667-680; Park K D, Kim Y S, Han D K, Kim Y H, Lee E H, Suh H, Choi K S. Biomaterials 1998; 19:851-859; Suggs L T, West J L, Mikos A G. Biomaterials 1999; 20:683-690; herein incorporated by reference in their entireties). Various copolymerization methods (Zakir M. O. Rzaev, Sevil Dincer, Erhan P. Prog Polym Sci 2007; 32:534-59) have been developed to synthesize the double double hydrophilic copolymers such as PEG-b-PNIPA (Zhu P W, Napper D R Macromolecules 1999; 32:2068-2070; Zhu P W, Napper D H. Langmuir 2000; 16:8543-8545; Zhang W Q, Shi L Q, Wu K, An Y L. Macromolecules 2005; 38:5743-5747; herein incorporated by reference in their entireties) or PEG-g-PNIPA (Qiu X, Wu C. Macromolecules 1997; 30:7921-7926; Virtanen J, Baron C, Tenhu H. Macromolecules 2000; 33:336-341; herein incorporated by reference in their entireties) by modifying PEG end-groups such as PEG-Br or amino-terminated PEG as macroinitiator or PEO methacrylate as macromonomer. The solubilizing effect of PEG on the shrinking backbone can compete with hydrophobic interactions in poly(NIPA) due to dehydration at a temperature above 35° C. (Bar A, Ramon O, Cohen Y, Mizrahi S. J Food Eng 2002; 55:193-199).
Thermoresponsive materials such as PNIPAM-derivatized gelatin (PNIPAM-gelatin) (Matsuda T. Jpn J Artif Organs 1999; 28:242-245) and PNIPA-derivatized hyaluronic acid (PNIPAM-HA) (Ohya S, Nakayama Y, Matsuda T. Jpn J Artif Organs 2000; 29:446-451; herein incorporated by reference in its entirety) have been functioned as cell-adhesive and cell non-adhesive matrix to encapsulate bovine smooth muscle cells for cell therapies; however, the entrapped cells died in hydrogel (Ohya, Nakayama, Matsuda. J Artif Organs 2001; 4:308-314; herein incorporated by reference in its entirety).